Feasibility of atmospheric cold plasma for the elimination of food hazards: Recent advances and future trends.

In recent decades, food safety has emerged as a worldwide public health issue with economic and political implications. Pesticide residues, mycotoxins, allergens, and antinutritional factors are the primary concerns associated with food products due to their potential adverse health effects. Although various conventional processing methods (such as washing, peeling, and cooking) have been used to reduce or eliminate these hazards from agricultural food materials, the results obtained are not quite satisfactory. Recently, atmospheric cold plasma (ACP), an emerging low -temperature and green processing technology, has shown great potential for mitigating food hazards. However, detailed descriptions of the effects of ACP treatment on food hazards are still not available. Thus, the current review aims to highlight recent studies on the efficacy and application of ACP in the reduction or elimination of pesticide residues, mycotoxins, allergens, and antinutritional factors in various food products. The possible working mechanisms of ACP and its effect on food quality, and the toxicity of degradation products are emphatically discussed. In addition, multiple factors affecting the efficacy of ACP are summarized in detail. At the same time, the major technical challenges for practical application and future development prospects of this emerging technology are also highlighted.

KRAS G12V mutation upregulates PD-L1 expression via TGF-ß/EMT signaling pathway in human non-small-cell lung cancer.

Although clinical data suggest remarkable promise for targeting programmed cell death protein-1 (PD-1) and ligand (PD-L1) signaling in non-small-cell lung cancer (NSCLC), it is still largely undetermined which subtype of patients will be responsive to checkpoint blockade. In the present study, we explored whether PD-L1 was regulated by mutant Kirsten rat sarcoma viral oncogene homolog (KRAS), which is frequently mutated in NSCLC and results in poor prognosis and low survival rates. We verified that PD-L1 levels were dramatically increased in KRAS mutant cell lines, particularly in NCI-H441 cells with KRAS G12V mutation. Overexpression of KRAS G12V remarkably elevated PD-L1 messenger RNA and protein levels, while suppression of KRAS G12V led to decreased PD-L1 levels in NCI-H441 cells. Consistently, higher levels of PD-L1 were observed in KRAS-mutated tissues as well as tumor tissues-derived CD4+ and CD8+ T cells using a tumor xenograft in B-NDG mice. Mechanically, both in vitro and in vivo assays found that KRAS G12V upregulated PD-L1 via regulating the progression of epithelial-to-mesenchymal transition (EMT). Moreover, pembrolizumab activated the antitumor activity and decreased tumor growth with KRAS G12V mutated NSCLC. This study demonstrates that KRAS G12V mutation could induce PD-L1 expression and promote immune escape via transforming growth factor-ß/EMT signaling pathway in KRAS-mutant NSCLC, providing a potential therapeutic approach for NSCLC harboring KRAS mutations.

Association between the HLA-B*1502 gene and mild maculopapular exanthema induced by antiepileptic drugs in Northwest China.

BACKGROUND: The relationship between the HLA-B*1502 gene and maculopapular exanthema (MPE) induced by antiepileptic drugs (AEDs) has not yet been elucidated. In this study, we investigated the association between AED-induced MPE (AED-MPE) and the HLA-B*1502 gene in patients in Northwest China. METHODS: We enrolled 165 subjects including nine patients with AED-MPE and 156 AED-tolerant patients as controls. HLA-B*1502 gene polymorphism was detected using digital fluorescence molecular hybridization (DFMH). The results of HLA genotyping were expressed as positive or negative for the HLA-B*1502 allele. An analysis of AED-MPE risk factors was performed using binary logistic regression, and differences in genotype frequencies between groups were assessed with the continuity correction chi-square test. RESULTS: We found that the HLA-B*1502 gene was a risk factor for AED-MPE (P = 0.028). The incidence of MPE induced by the two types of AEDs was different, and the incidence of aromatic AEDs use was higher that of non-aromatic AEDs use (P = 0.025). The comparison of the gene frequencies of the HLA-B*1502 allele between the two groups taking aromatic AEDs was also statistically significant (P = 0.045). However, there were no significant differences in terms of age, gender, ethnicity, or region in patients with MPE induced by AEDs. In addition, no association between the HLA-B1502 allele and CBZ- or OXC-induced MPE was found. CONCLUSIONS: In northwestern China, the HLA-B*1502 allele was associated with aromatic AED-MPE. Since MPE can develop into Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN), the HLA-B*1502 gene should be evaluated before administering AEDs.

Effect of rosemary extract on lipid oxidation of cooked pork during simulated gastric digestion.

BACKGROUND: Oxidation of food lipids occurs in the gastrointestinal tract, resulting in potential adverse health effects. Rosemary extract (RE), as one of the most popular naturally sourced antioxidants, is widely used in the food industry. However, the effect of RE on lipid oxidation during gastrointestinal digestion has not been well investigated. Therefore, this study aimed to evaluate the effect of RE on lipid oxidation of cooked pork during simulated gastric digestion. RESULTS: Results showed that RE at 12.5, 25, 50, and 100 mg kg-1 pork effectively decreased the formation of malondialdehyde during simulated gastric digestion of cooked pork. RE also effectively mitigated the decline of fatty acids during the simulated gastric digestion of pork. The total phenolic content in RE was calculated to be 170.67 mg gallic acid equivalent (GAE) g-1 . RE dissolved in distilled water (pH 6.5) or potassium hydrogen phthalate-hydrochloric acid buffer solution (0.2 mol L-1 , pH 3.0) both exhibited strong 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and 1,1-diphenyl-2-picrylhydrazyl radical-scavenging activities as well as ferric reducing capacity. The inhibitory effects of RE on lipid oxidation of cooked pork during simulated gastric digestion may be attributed to the phenolic compounds with antioxidant properties. CONCLUSION: The results lend support to the possible application of rosemary or RE as a rich source of natural antioxidants to inhibit the oxidation of food lipids during gastrointestinal digestion. © 2019 Society of Chemical Industry.

Adenosine induces apoptosis through TNFR1/RIPK1/P38 axis in colon cancer cells.

Adenosine, a metabolite of ATP, ubiquitously exists in a wide range of organs and tissues. We previously reported that adenosine was implicated in apoptosis in many cancer cells by extrinsic and/or intrinsic pathways. Here, we found that adenosine suppresses the cell growth by induction of apoptosis of human colonic cancer cells through a novel mechanism. Adenosine suppresses the cell growth of human SW620 and SW480 colon cells in an adenosine transporter and adenosine kinase dependent manner. Moreover, the cell growth suppression is induced by apoptosis through activation of caspase-3 and PARP, and accumulation of ROS in cells. Importantly, we found that adenosine increases the expression of TNFR1 and RIPK1 and the phosphorylation of p38. Knockdown of TNFR1 or RIPK1 impairs the activation of p38, blocks the cleavage of PARP, and provides partially, yet significantly protection from cell death, including reducing the ROS generation in the colon cancer cells. These results indicate that a TNFR1/RIPK1/P38 axis is present in adenosine-induced apoptosis of colonic cancer cells. This axis triggers apoptosis and plays crucial roles in relay of the death signaling. Our study also provides additional experimental evidence for adenosine as a potent therapeutic drug in cancer therapy.

Population Structure of the Late Blight Pathogen Phytophthora infestans in a Potato Germplasm Nursery in Two Consecutive Years.

As the causal agent of late blight on potato, Phytophthora infestans is one of the most destructive plant pathogens worldwide and widely known as the Irish potato famine pathogen. Understanding the genetic structure of P. infestans populations is important both for breeding and deployment of resistant varieties and for development of disease control strategies. Here, we investigate the population genetic structure of P. infestans in a potato germplasm nursery in northwestern China. In total, 279 isolates were recovered from 63 potato varieties or lines in 2010 and 2011, and were genotyped by mitochondrial DNA haplotypes and a set of nine simple-sequence repeat markers. Selected isolates were further examined for virulence on a set of differential lines containing each resistance (R) gene (R1 to R11). The overall P. infestans population was characterized as having a low level of genetic diversity and resistance to metalaxyl, and containing a high percentage of individuals that virulent to all 11 R genes. Both A1 and A2 mating types as well as self-fertile P. infestans isolates were present but there was no evidence of sexual reproduction. The low level of genetic differentiation in P. infestans populations is probably due to the action of relatively high levels of migration as supported by analysis of molecular variance (P < 0.01). Migration and asexual reproduction were the predominant mechanisms influencing the P. infestans population structure in the germplasm nursery. Therefore, it is important to ensure the production of pathogen-free potato seed tubers to aid sustainable production of potato in northwestern China.

Carnosic acid induces apoptosis associated with mitochondrial dysfunction and Akt inactivation in HepG2 cells.

Carnosic acid (CA), a phenolic diterpene isolated from rosemary, shows potential benefits in health promotion and disease prevention. In the present study, the cytotoxic and apoptotic-inducing effects of CA on human hepatocellular carcinoma HepG2 cells were investigated. The MTT assay results indicated that CA decreased cell viability in HepG2 cells in a dose-dependent manner. Treatment with CA caused a rapid Caspase-3 activation and subsequently proteolytic cleavage of poly (ADP-ribose) polymerase (PARP), both of which were markers of cells undergoing apoptosis. CA also dissipated mitochondrial membrane potential and decreased the ratio of Bcl-2/Bax protein, which mediated cytosolic translocation of cytochrome c from the mitochondria. Furthermore, CA reduced the phosphorylation of Akt, which was partially inhibited by insulin, an activator of phosphatidylinositol 3-kinase (PI3K)/Akt signalling pathway. In conclusion, our data suggest that the mitochondrial dysfunction and deactivation of Akt may contribute to the apoptosis-inducing effects of CA.

Adenosine induces apoptosis in human liver cancer cells through ROS production and mitochondrial dysfunction.

Mitochondria are the most important sensor for apoptosis. Extracellular adenosine is well reported to induce apoptosis of tumor cells. Here we found that extracellular adenosine suppresses the cell growth by induction of apoptosis in BEL-7404 liver cancer cells, and identified a novel mechanism that extracellular adenosine triggers apoptosis by increasing Reactive Oxygen Species (ROS) production and mitochondrial membrane dysfunction in the cells. We observed that adenosine increases ROS production, activates c-Caspase-8 and -9 and Caspase effectors, c-Caspase-3 and c-PARP, induces accumulation of apoptosis regulator Bak, decreases Bcl-xL and Mcl-1, and causes the mitochondrial membrane dysfunction and the release of DIABLO, Cytochrome C, and AIF from mitochondria to cytoplasm in the cells; ROS inhibitor, NAC significantly reduces adenosine-induced ROS production; it also shows the same degree of blocking adenosine-induced loss of mitochondrial membrane potential (MMP) and apoptosis. Our study first observed that adenosine increases ROS production in tumor cells and identified the positive feedback loop for ROS-mediated mitochondrial membrane dysfunction which amplifies the death signals in the cells. Our findings indicated ROS production and mitochondrial dysfunction play a key role in adenosine-induced apoptosis of 7404 cells.

Screening and verification of ssDNA aptamers targeting human hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most malignant cancers in the world. Molecular probes that can recognize biomarkers specific for HCC are urgently needed to improve the sensitivity and specificity of early diagnosis. A recent study has applied the method of systematic evolution of ligands by exponential enrichment and produced several aptamers that can bind specifically to mouse liver cancer cells and tissues. However, the binding affinity to human liver cancer has not been fully identified. Using human-derived hepatoma cell line HepG2 as positive target cell line and normal hepatocyte cell line HL-7702 as negative one, we obtained an aptamer HA09 that could specifically bind to human liver cancer cells with Kd in the nanomolar range and recognize paraffin-embedded human HCC tissues. This aptamer may facilitate the discovery of novel biomarkers and serve as an ideal molecular probe for intracellular delivery with both diagnostic and therapeutic implications.

Induction of senescence by adenosine suppressing the growth of lung cancer cells.

Extracellular adenosine is well reported to suppress tumor growth by induction of apoptosis. However, in this study we found that adenosine treatment results in cellular senescence in A549 lung cancer cells both in vitro and in vivo; adenosine induces cell cycle arrest and senescence in a p53/p21 dependent manner; adenosine elevates the level of phosphor-γH2AX, pCHK2 and pBRCA1, the markers for prolonged DNA damage response which are likely responsible for initiating the cellular senescence. Our study first demonstrates that adenosine suppresses growth of cancer cells by inducing senescence and provides additional evidence that adenosine could act as an effective anticancer agent for targeted cancer therapy.

Lauric arginate ethyl ester: An update on the antimicrobial potential and application in the food systems.

Lauric arginate ethyl ester (LAE), a cationic surfactant with low toxicity, displays excellent antimicrobial activity against a broad range of microorganisms. LAE has been approved as generally recognized as safe (GRAS) for widespread application in certain foods at a maximum concentration of 200 ppm. In this context, extensive research has been carried out on the application of LAE in food preservation for improving the microbiological safety and quality characteristics of various food products. This study aims to present a general review of recent research progress on the antimicrobial efficacy of LAE and its application in the food industry. It covers the physicochemical properties, antimicrobial efficacy of LAE, and the underlying mechanism of its action. This review also summarizes the application of LAE in various foods products as well as its influence on the nutritional and sensory properties of such foods. Additionally, the main factors influencing the antimicrobial efficacy of LAE are reviewed in this work, and combination strategies are provided to enhance the antimicrobial potency of LAE. Finally, the concluding remarks and possible recommendations for the future research are also presented in this review. In summary, LAE has the great potential application in the food industry. Overall, the present review intends to improve the application of LAE in food preservation.

Curcumin Inhibits the Proliferation of Renal Cancer 786-O Cells through MTOR Signaling Pathway and Its Mechanism.

Objectives: The mechanism of curcumin inhibiting renal cancer 786-O cells proliferation through MTOR signaling pathway was investigated. Methods: Human renal cancer 786-O cells were cultured with curcumin for 48 h. The OD values were measured by the MTT method, and the growth inhibition rate of 786-O cells was calculated. The cell cycle distribution and apoptosis rate were detected by flow cytometry (FCM). Transwell chamber was introduced to detect cell invasion ability. Cell migration ability was detected by the cell scratch test. The protein expression was assessed by Western blot. Results: With curcumin concentration increasing, the expressions of MMP2, MMP9, MTOR, and p-MTOR proteins and the number of cells in the S phase decreased gradually, while number of cells in G1 and G2/M phases and cells apoptosis rate increased continuously. With the increasing of concentration and time, growth of 786-O cells in each treatment group was inhibited to varying degrees. The higher the inhibition rate was, the cells migration and transmembrane cells proportion decreased significantly. Conclusions: Curcumin inhibits the proliferation, migration, and invasion and induces apoptosis of renal cancer 786-O cells by blocking the MTOR signaling pathway. It may be related to the downregulation of MMP2 and MMP9 proteins.

Hsa_circ_0003288 facilitates tumor progression by targeting miR-145 in non-small cell lung cancer cells.

Circular RNA (circRNA) has been shown to participate in various tumors, including lung cancer. In the present study, we explored the expression and functional relevance of hsa_circ_0003288 in human non-small cell lung cancer (NSCLC). We verified that hsa_circ_0003288 expression was upregulated in lung cancer tissues and cell lines. Overexpression of hsa_circ_0003288 dramatically promoted lung cancer cell proliferation, colony formation, inhibited apoptosis, and increased cell migration and invasion in vitro. Xenograft experiments showed that hsa_circ_0003288 overexpression accelerated tumor growth in vivo. Mechanistically, hsa_circ_0003288 negatively regulated miR-145 to exert the oncogenic role in lung cancer. Overexpression of miR-145 decreased cell proliferation, induced apoptosis, and suppressed migration and invasion in lung cancer. Additionally, miR-145 co-transfection abolished the oncogenic role of hsa_circ_0003288. Collectively, these findings identified a novel regulatory role of hsa_circ_0003288/miR-145 axis in the progression of NSCLC.

Synergistic Inactivation Mechanism of Combined Plasma-Activated Water and Mild Heat against Saccharomyces cerevisiae.

ABSTRACT: This study aimed to elucidate the mechanism of synergistic inactivation of Saccharomyces cerevisiae by the combined use of plasma-activated water (PAW) and mild heat (40 to 50°C). A reduction of 4.40 log CFU/mL in S. cerevisiae was observed after the synergistic combination of PAW and mild heat at 50°C for 6 min, whereas the individual treatments of PAW at 25°C and mild heat at 50°C for 6 min resulted in a reduction of 0.27 and 1.92 log CFU/mL, respectively. The simultaneous application of PAW and mild heat caused significant increases in membrane permeability, resulting in the leakage of intracellular components (such as nucleic acids and proteins) and increased uptake of propidium iodide. The combined treatment of PAW and mild heat also resulted in significant increases in the intracellular levels of reactive oxygen species and disruption of mitochondrial membrane potential in S. cerevisiae cells. In summary, this study illustrates the potential of PAW treatment combined with mild heat to rapidly inactivate microorganisms in food products.

Pharmacokinetics and tissue distribution study of liposomal albendazole in naturally Echinococcus granulosus infected sheep by a validated UPLC-Q-TOF-MS method.

Albendazole (ABZ) is the first-line drug in treating echinococcosis, which is recommended by WHO. To address the poor bioavailability of albendazole, liposomal albendazole was formulated and is available in our hospital for many years. In this study, a sensitive, reliable and accurate UPLC-Q-TOF-MS method was developed and validated for the determination of albendazole and its metabolites, albendazole sulfoxide (ABZSO), albendazole sulfone (ABZSO2) and albendazole-2-aminosulfone (ABZSO2NH2) in naturally echinococcus granulosus (E. granulosus) infected sheep plasma and tissues with mebendazole (MBZ) as the internal standard (IS). Plasma and tissues samples were prepared by protein precipitation method. The separation was performed on an ACQUITY UPLC® BEH C18 column (2.1 × 50 mm, 1.7 µm) with a gradient mobile phase consisting of methanol and water containing 0.1% formic acid at 0.4 mL/min. The detection was performed on a quadrupole time-of-flight (Q-TOF) high-resolution mass spectrometer using positive electrospray ionization (ESI) source with a chromatographic run time of 6.0 min. The detection was operated using target ions of [M + H]+ at m/z 266.096 for ABZ, m/z 282.091 for ABZSO, m/z 298.086 for ABZSO2, m/z 240.081 for ABZSO2NH2 and m/z 296.104 for IS in selective ion mode, respectively. This method was validated in terms of selectivity, linearity, precision, accuracy, recovery, matrix effect, dilution effect, carryover effects, stability, calibration curve and LLOQ. All validation parameter results were within the acceptable range described in guideline for bioanalytical method validation. This method has been successfully applied to the pharmacokinetic study following single and multiple oral dose of 10 mg/kg liposomal albendazole, and tissue distribution study following multiple oral dose of 10 mg/kg, with emulsion albendazole as the reference preparation. The results in the article will provide valuable information for use in clinical applications of liposomal albendazole and also be beneficial for further development of liposomal albendazole in future studies.

Augmenting the therapeutic efficacy of adenosine against pancreatic cancer by switching the Akt/p21-dependent senescence to apoptosis.

BACKGROUND: There are many reports of the anti-tumour effects of exogenous adenosine in gastrointestinal tumours. Gemcitabine, a first line agent for patients with poor performance status, and adenosine have structural similarities. For these reasons, it is worth exploring the therapeutic efficacy of adenosine and its underlying mechanism in pancreatic cancer. METHODS: Tumour volumes and survival periods were measured in a patient-derived xenograft (PDX) model of pancreatic cancer. The Akt-p21 signalling axis was blocked by p21 silencing or by the Akt inhibitor GSK690693. The combined effect of GSK690693 and adenosine was calculated by the Chou-Talalay equation and verified by measuring fluorescent areas in orthotopic models. FINDINGS: Among the PDX mice, the tumour volume in the adenosine treatment group was only 61% of that in the saline treatment group. Adenosine treatment in combination with the Akt inhibitor, GSK690693, or the silencing of p21 to interfere with the Akt-p21 axis can switch the senescence-to-apoptosis signal and alleviate drug resistance. A GSK690693-adenosine combination caused 37.4% further reduction of tumour fluorescent areas in orthotopic models compared with that observed in adenosine monotherapy. INTERPRETATION: Our data confirmed the therapeutic effect of adenosine on pancreatic cancer, and revealed the potential of Akt inhibitors as sensitization agents in this treatment. FUND: The work is supported by grants from the National Natural Science Foundation of China to Dongqin Yang (81572336, 81770579) and Jie Liu (81630016, 81830080), and jointly by the Development Fund for Shanghai Talents (201660).

STAT3 activation in tumor cell-free lymph nodes predicts a poor prognosis for gastric cancer.

STAT3 is constitutively activated in many human cancers including gastric cancer and plays crucial roles in modulating cancer cell proliferation, survival, metastasis as well as the microenvironment of pre-metastatic niches. Accumulating evidence has implicated STAT3 as a promising target for cancer therapy and it has been well established that tumor cell metastasized to lymph node is associated with poor prognosis. However, little is known about the relation between STAT3 activation in tumor cell-free lymph nodes and patient clinical outcomes. The objective of the current study was to investigate the role of STAT3 activity in tumor cell-free lymph nodes in tumor progression and prognosis for gastric cancer patients. Immunohistochemical analyses for p-STAT3, Ki-67, CD68 and Bcl-xL were performed in tumor cell-free lymph nodes from 60 gastric cancer patients. Survival analysis was conducted by using the Kaplan-Meier method. Immunohistochemical analyses showed that hyperactivity of STAT3 in tumor cell-free lymph nodes was significantly associated with tumor recurrence, and STAT3 activation pattern coincides with expression Ki-67, CD68, Bcl-xL. Survival analysis revealed that persistent STAT3 activation in uninvolved lymph nodes was positively associated with poor overall survival (P<0.05). These findings suggest that STAT3 activation in tumor-free lymph nodes is involved in the pathogenesis and metastasis of gastric cancer and that elevated STAT3 activity in lymph nodes prior to tumor cell arrival may indicate a poorer prognosis. These clinical studies support our findings in mouse tumor models showing that STAT3 activation is crucial for pre-metastatic niche formation and metastasis.

Association study of miR­149 rs2292832 and miR­608 rs4919510 and the risk of hepatocellular carcinoma in a large­scale population.

Polymorphisms in pre­microRNAs (miRNAs) or mature miRNAs may influence miRNA processing or target binding, thus contributing to tumorigenesis and cancer development. The present study aimed to evaluate whether miR­149 rs2292832 (C>T) and miR­608 rs4919510 (G>C) are associated with the risk and clinical characteristics of hepatocellular carcinoma (HCC) in a large­scale population. miR­149 rs2292832 and miR­608 rs4919510 were genotyped in a total of 993 patients with HCC and 992 unrelated healthy subjects by Sequenom MassARRAY. The results showed that, compared with the reference CC genotype, the TC+TT genotype of miR­149 was more highly associated with HCC [CC vs. TC+TT: Odds ratio (OR)=1.384, 95% confidence interval (CI)=1.013­1.892, P=0.041], and was also associated with an increased risk of hepatitis B virus (HBV)­associated HCC (CC vs. TC+TT: OR=1.453, 95% CI=1.034­2.042, P=0.031). However, no significant association between miRNA­608 rs4919510 and the risk of HCC/HBV­associated HCC was found. In addition, these two SNPs were shown not to be correlated with a range of clinical characteristics. The present study may provide an indicator for identification of the high risk of HCC in patients.